The present invention relates to oximeters for spectro-photometric in-vitro determination of hemoglobin derivatives and at least one further analyte in a sample.
Currently available oximeters mainly use incandescent lamps as measurement light sources. In “Technical Aspects of Bilirubin Determination in Whole Blood”; HALLEMANN et al.; Point of Care Volume 4, Number 1, March 2005, an oximeter module of a blood gas analyzer (OMNI Blood Gas Analyzer) is described, in which bilirubin is spectroscopically determined as an additional analyte beside hemoglobin derivatives. A halogen lamp with a broad spectral range is used as a measurement light source.
From JP 2004-108781 a spectroscope has become known, in which prior to irradiation into a sample, light emitted by a white light LED is split into its spectral components by means of two diffraction gratings and is then radiated into the sample through a projection slit, in order to determine an analyte in a sample, for instance. Variants based on a transmission geometry as well as variants based on a reflection geometry are described, where the intensity of transmitted or reflected light is measured in temporal sequence for each wavelength. A disadvantage of this known spectroscope is the time-consuming recording of a spectrum by means of the two diffraction gratings, which split the measuring light into its spectral components.
From U.S. Pat. Appln. Pub. No. 2005/0154277 A1 a miniaturized “in-vivo” spectroscope is known, which can be used inside the body for instance to detect hemorrhages in the gastrointestinal tract by means of spectral analysis of the hemoglobin derivatives present. LEDs may be used as light source.
Furthermore, use of a non-invasive oximeter is known from U.S. Pat. Appln. Pub. No. 2005/0267346 A1, where light is radiated into blood-filled tissue of a fingertip or earlobe, and the composition of the blood (oxygen saturation) is inferred from light-absorption in the blood using a transmitted-light or reflected-light method. A white light LED can be used as light source, but filters or diffraction gratings must be used prior to irradiation to select defined wavelengths for irradiation into the tissue.
From U.S. Pat. No. 6,262,798 B1 an oximetric method for measuring non-hemolyzed blood is known. In this measurement method a plurality of defined, monochromatic wavelengths are sequentially radiated into the sample, arrays of varicolored LEDs or conventional white light lamps being used from which defined wavelengths are filtered by means of a monochromator, which are then radiated into the sample.
In “Blood gases and oximetry: calibration-free new dry-chemistry and optical technology for near-patient testing”; Boalth et al.; Clinica Chimica Acta 307 (2001) 225-233, a spectrophotometric system for in-vitro oximetry is described, which works with a white light LED as light source. For the determination of hemoglobin derivatives the wavelength band of 470-670 nm is recorded by means of a 128-channel-linear-CCD-array and used for evaluation. This wavelength range exceeds the wavelength range conventionally used for determination of hemoglobin derivatives, thus offering the possibility of correcting the values of hemoglobin derivatives for bilirubin as an interfering substance, which overlays hemoglobin absorption in parts of the range. The enlarged wavelength range is only used for correcting the hemoglobin derivatives to be determined, but not for determining bilirubin as an additional analyte.
To produce polychromatic light by means of LEDs, it has become known to use luminescence conversion LEDs having one or more primary emission wavelengths, which are modified by luminescence conversion layers such that broad-band polychromatic light will be radiated as a result. Such light sources are for instance described in U.S. Pat. Appln. Pub. No. 2005/0127385 A1. The radiated polychromatic light is in this case composed of a short-wave spectral region of the primary emission wavelengths emitted by at LED-chip as primary emitter, and a spectral region of longer wavelengths radiated by dye layers excited by the primary emission of the LED as secondary emitters.
U.S. Pat. No. 6,809,347 B2 describes a white light LED which includes a LED emitting blue or UV-light and a superposed luminophore layer which absorbs part of the blue or UV-light emitted by the LED and subsequently emits light in the long-wave spectral region, thus producing white light by superposition, whose spectral characteristics can be defined by modification of the luminophore layer.
Finally, EP 1 473 771 A1 describes an alternative design of a white light LED, which consists of a plurality of at least partially transparent light-emitting LED layers of different emission wavelengths, which are stacked one above the other in such a way that the individual emission wavelength bands are superposed in radiation direction and white light is emitted as a result.